ArticleNature medicine2015
Isocitrate dehydrogenase 1 and 2 mutations induce BCL-2 dependence in acute myeloid leukemia.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 357 papers.
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Who cites it
357 citing papers in PubMed, 567 citations in OpenAlex.
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- AI-enabled multi-omics pharmacogenomic modeling guides resistance-aware multitarget optimization of venetoclax therapy in acute myeloid leukemia.NPJ precision oncology · 2026Article
- Synthetic lethality in TP53-mutant acute myeloid leukemia.Blood advances · 2026Article
- Defining and managing high-risk acute myeloid leukemia (AML) in 2026.Annals of hematology · 2026Review
- Premature senescence impairs hematopoietic stem cell function during sickle cell disease in mice and humans.Science translational medicine · 2026Article
- Modern Concepts in Precision Targeting of Acute Myeloid Leukemia Based on Principles of Molecular Oncology.Cancers · 2026Review
- Chromosomal rearrangement-enhanced mRNA stability drives the oncogenic potential of fusion genes in pediatric leukemia.Haematologica · 2026Article
- Oncometabolite 2-hydroxyglutarate destabilizes CDH1 to regulate quiescence and enhance chemotherapy sensitivity.Cell communication and signaling : CCS · 2026Article
- Anti-apoptotic BCL-2 family proteins: from regulatory networks to therapeutic targeting.Oncogenesis · 2026Review
- Mitochondrial RNA degradation regulates differentiation, stemness, and immune sensitivity in acute myeloid leukemia.Nature communications · 2026Article
- Silver bullets for the golden age: treatingHaematologica · 2026Article
- Targeting "undruggable" cancer proteins: pharmacological challenges and emerging strategies.Translational cancer research · 2026Review
- Real-life multicenter experience of long-term treatment with venetoclax plus azacitidine for acute myeloid leukemia in China.Scientific reports · 2026Article
- SLC25A1 reprograms mitochondrial and fatty acid metabolism to promote the progression of acute myeloid leukemia.Haematologica · 2026Article
- Isocitrate dehydrogenase mutations as potential tumour agnostic targets.EJC supplements : EJC : official journal of EORTC, European Organization for Research and Treatment of Cancer ... [et al.] · 2026Article
- Biomarkers and advances in AML-MRC: from bench to bedside.Annals of hematology · 2026Review
297 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Mutant isocitrate dehydrogenase (IDH) 1 and 2 proteins alter the epigenetic landscape in acute myeloid leukemia (AML) cells through production of the oncometabolite (R)-2-hydroxyglutarate (2-HG). Here we performed a large-scale RNA interference (RNAi) screen to identify genes that are synthetic lethal to the IDH1(R132H) mutation in AML and identified the anti-apoptotic gene BCL-2. IDH1- and IDH2-mutant primary human AML cells were more sensitive than IDH1/2 wild-type cells to ABT-199, a highly specific BCL-2 inhibitor that is currently in clinical trials for hematologic malignancies, both ex vivo and in xenotransplant models. This sensitization effect was induced by (R)-2-HG-mediated inhibition of the activity of cytochrome c oxidase (COX) in the mitochondrial electron transport chain (ETC); suppression of COX activity lowered the mitochondrial threshold to trigger apoptosis upon BCL-2 inhibition. Our findings indicate that IDH1/2 mutation status may identify patients that are likely to respond to pharmacologic BCL-2 inhibition and form the rational basis for combining agents that disrupt ETC activity with ABT-199 in future clinical studies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.